In the airway, the autonomic nervous system controls smooth muscle tone, secretion by glands, and blood flow. Although there is abundant physiological and pharmacological evidence indicating that dysfunction of this autonomic control of the airways contributes to the causes and symptoms of pulmonary diseases such as bronchial asthma, chronic obstructive pulmonary disease and emphysema, little is actually known about the regulation of these nerves. Our long term goal is to provide knowledge of how autonomic tone is regulated in the airway, especially that provided by the parasympathetic nervous system. Control of smooth muscle in the trachea and bronchi is predominantly by nerve fibers that emanate from neuronal cell bodies in parasympathetic ganglia, small clusters of cell bodies located near the airway wall. The parasympathetic tone of the airway smooth muscle is thought to be under the control of the central nervous system where signals are transmitted rhythmically during respiration to the parasympathetic neurons in the airway wall. This signal activates airway parasympathetic ganglia neurons by release of a neurotransmitter which mediates cholinergic synaptic transmission in the ganglia. Separate, but potentially important, forms of neural regulation of parasympathetic neurons in the airways are by the so-called local peripheral reflex pathway and the intraganglionic pathways. In the peripherals reflex pathway, a sensory nerve is activated by changes in the airway and communicates directly with the parasympathetic neuron in the nearby ganglia by releasing neuropeptides from branches of the sensory axon, evoking non-cholinergic synaptic transmission. In other words, this is an sensory- parasympathetic reflex, independent of the central nervous system. A peripheral reflex would thus allow local increases in parasympathetic tone in an airway segment, independent of changes in another segment. In the intraganglionic pathway, postganglionic axons leaving a bronchial ganglion serve to innervate, and modulate the function of neighboring ganglia within the airway tree. This proposal describes experiments that will address our central hypothesis, namely that the parasympathetic nerve activity in the airways is shaped by the integration of three separate inputs: 1.) input from the central nervous system {classical cholinergic nicotinic input), 2.) input from the peripheral reflex sensory fibers, and 3.) input from surrounding postganglionic parasympathetic ganglia. We feel that an understanding of the mechanism of this integration is a prerequisite to obtaining knowledge on the mechanisms by which airway neurophysiology is regulated in health and disregulated in disease.